KIT protein expression and mutational status of KIT gene in pituitary adenomas

Olivera Casar-Borota1, Stine Lyngvi Fougner, Jens Bollerslev

  • 1Faculty of Medicine, University of Oslo, 0027 Oslo, Norway. olivera.casar.borota@medbio.umu.se

Insights

KIT protein, a target for cancer therapy, is expressed in over half of pituitary adenomas. Researchers found no KIT gene mutations in these tumors, suggesting further investigation into Imatinib Mesylate treatment for specific pituitary adenomas.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • KIT protein and KIT gene mutations are studied in various tumors, especially since the development of KIT/PDGFRA tyrosine kinase inhibitors like Imatinib Mesylate.
  • Previous research on KIT expression in pituitary adenomas is limited, with no studies investigating the mutational status of the KIT gene in these tumors.

Purpose of the Study:

  • To investigate KIT protein expression and KIT gene mutational status in pituitary adenomas.
  • To determine if KIT expression correlates with specific pituitary adenoma subtypes or clinical data.
  • To explore the potential for KIT-targeted therapies in pituitary adenomas.

Main Methods:

  • Immunohistochemistry was used to assess KIT protein expression in 252 pituitary adenomas.
  • Western blot analysis confirmed KIT expression in a subset of 48 adenomas.
  • Exons 9, 11, 13, and 17 of the KIT gene were analyzed for mutations using denaturing high-performance liquid chromatography and sequencing.

Main Results:

  • KIT protein was expressed in 52.4% (cytoplasmic) and 8.3% (membranous) of pituitary adenomas.
  • Significant differences in KIT expression were observed between non-functioning, growth hormone-producing, and adrenocorticotropic hormone-producing adenomas.
  • No mutations were detected in the examined exons of the KIT gene in any of the analyzed pituitary adenomas.

Conclusions:

  • KIT protein expression is present in a significant subset of pituitary adenomas, with varying patterns depending on adenoma type.
  • The absence of KIT gene mutations suggests that KIT's role in pituitary adenoma pathogenesis may not involve direct mutation.
  • Further research is warranted to determine if pituitary adenomas with KIT expression could respond to Imatinib Mesylate treatment.

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...